Setting reference intervals, urine dipstick confirmation, and background stain on Western blotting - Tips From the Clinical Experts
Categories: Child Care and Health TipsQ: Does every laboratory need to set its own reference values, or can it use “values” from the literature? Do you know any article about making reference values for blood gas analyses? How many patients need to be included in a study of reference values?
A: The concept of reference intervals is evolving. Although traditionally laboratories have based reference intervals on values obtained from “healthy” individuals, for an increasing number of tests (such as cholesterol, glucose, and PSA), reference limits are based on risk of disease as determined from outcome studies. At present, however, most reference limits are still defined in the traditional fashion.
The most widely accepted document of reference values is that published by the NCCLS (Wayne, PA). (1) To establish reference limits with reasonable accuracy, it is necessary to use a sample size of at least 1120 individuals. If it is necessary to “partition” the reference interval (for example, for children and adults, or for males and females), it is necessary to use 120 individuals for each group. In the United States, regulatory agencies do not require laboratories to establish their own reference intervals, but to validate the values that they use (these can be derived from publications, the manufacturer, or other laboratories in the area). The NCCLS document suggests the use of 20 individuals to validate reference limits; if no more than two are outside the reference interval, then the proposed limits are valid for the laboratory. We have found that in our laboratory, which serves a somewhat unique population, that we can validate most reference limits, but we need to establish our own in about 10 percen t to 20 percent of cases.
With respect to blood gases, there have been relatively few studies cited over the last 30 years in Index Medicus covering reference values in populations other than neonates. One recent study by Crapo, et al. compared values at sea level and at an altitude of 1,400 m, using a total sample of 339 adults. (2) They found that partial pressure of oxygen declines gradually with increasing age.
Another study by Dong, et al. of arterialized capillary blood gases evaluated 712 normal individuals between the ages of 1 month and 24 years. (3) They found that partial pressures of oxygen and carbon dioxide were lower in infants and young children, reaching adult levels by 7 to 12 years of age.